The long-term objective of this research is to understand the mechanisms by which HIV regulates expression of its genes. This application will focus on the transcriptional regulation mediated by the HIV TAT protein and the cis-acting element known as TAR, an RNA element which interacts with Tat via a bulge and cellular factors via a loop. Dr. Garcia-Blanco has identified cellular trans-acting factors that regulate the HIV LTR, and has purified one of these, CA-150, which is required for Tat transactivation in vitro. The cDNA of CA-150 has been cloned and sequenced, and the results suggest that this protein is a transcription factor homologous with the yeast transcriptional coupler Gal11p. Dr. Garcia-Blanco proposes to (1) study the structure and function of CA-150; (2) identify and characterize factors physically and functionally associated with CA-150;, and (3) identify and characterize TAR loop binding proteins functionally relevant to transactivation of the HIV promoter. The results of these investigations could provide novel targets for anti-viral AIDS therapy.